PROJECT SUMMARY We are requesting to supplement our currently funded project, titled Evaluating Concomitant Use of Very Low Nicotine Content Cigarettes and E-cigarettes Among Daily and Non-Daily Smokers on Abuse Liability (R01DA042526). We wish to add a third arm to the study, one that exposes daily cigarette smokers to high and low nicotine dose JUUL (JUUL Labs Inc., San Francisco, CA) electronic cigarettes (e-cigs), along with the very low nicotine content cigarettes (VLNCCs), during Phases 3 & 4. In the parent study, smokers are provided with eGo-T e-cigs, which are 2nd generation devices. However, since we submitted the original grant proposal, the 4th generation JUUL device has captured over 75% of the U.S. e-cig market. Because of its ubiquity, we believe that by adding the JUUL device, we will be providing data on potential dual use of e-cigs and VLNCs of potentially greater value to the scientific and regulatory fields. At the time of this writing, we have randomized 140 DS and 14 ITS participants. In our previous progress report, we proposed to continue recruitment of both DS and ITS through the planned no-cost extension of this grant, which would result in an over-sampling of DS participants and provide sufficient time to recruit the 80 ITS we originally proposed (note that the NCE will be necessitated in part because while year 1 of this grant received full funding, it was shortened by 6 months to place it on a particular funding cycle). With the proposed supplement, we would continue our current recruitment strategy, but will now assign new DS participants to the JUUL condition, as noted below, on a 4:1 basis with the parent grant's assignment to the eGo-T E-cigs. The existing aims and design of the parent grant would be unchanged. We are requesting to add another arm that would use the same design and measures as the parent grant, with the only difference being that we will expose smokers to JUUL e-cigs, rather than to the eGo-T product we are currently using. We are proposing to assign newly recruited daily smokers to this new arm, where they will be exposed to high and low dose JUUL products, along with the VLNCCs. The new arm would be comprised of at least 80 daily smokers, similar to the other two arms of the parent grant.